CN103842817A - Fin-FET biosensor with improved sensitivity and selectivity - Google Patents

Fin-FET biosensor with improved sensitivity and selectivity Download PDF

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CN103842817A
CN103842817A CN201180057335.1A CN201180057335A CN103842817A CN 103842817 A CN103842817 A CN 103842817A CN 201180057335 A CN201180057335 A CN 201180057335A CN 103842817 A CN103842817 A CN 103842817A
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type fet
fin type
sensor
transistor
sample
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胡文闯
田如海
S.雷冈达
K.特里维迪
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TAXAS SYSTEM, University of, Regents of
University of Texas System
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    • H01L29/68—Types of semiconductor device ; Multistep manufacturing processes therefor controllable by only the electric current supplied, or only the electric potential applied, to an electrode which does not carry the current to be rectified, amplified or switched
    • H01L29/76—Unipolar devices, e.g. field effect transistors
    • H01L29/772—Field effect transistors
    • H01L29/78—Field effect transistors with field effect produced by an insulated gate
    • H01L29/785—Field effect transistors with field effect produced by an insulated gate having a channel with a horizontal current flow in a vertical sidewall of a semiconductor body, e.g. FinFET, MuGFET

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Abstract

The claimed invention is directed to a fin-FET biosensor with improved sensitivity and selectivity. Embodiments of the invention are also directed to fin-FET biosensor arrays, methods for operating fin-FET biosensors with improved sensitivity and selectivity, and methods of operating fin-FET biosensor arrays.

Description

There is improved sensitivity and specific fin type FET biology sensor
the cross reference of related application
The application requires the benefit of priority under 61/387,903 U.S.C. § 119 (e) of the U.S. Provisional Application of submitting on September 29th, 2010.
Technical field
The present invention relates generally to the electronic sensor of the field effect transistor (ISFET) based on toward ion-sensitive.More particularly, relate to and there is the fin type FET transistor of nanoscale width raceway groove as sensing element.
Background technology
Enzyme linked immunosorbent assay (ELISA) (ELISA) is the normally used test for medical diagnosis, and the existence of the molecular contaminants of test such as agricultural chemicals and water and food pollution thing.ELISA test is very sensitive (every milliliter of ~ pico-gram), but will spend a few hours operation by the technician of fine craftsmanship.In addition, ELISA test needs several order chemical reactions, and they are that the time is sensitive and process sensitive.Need expensive optical device to carry out reading result.
The field effect transistor (biological FET and ISFET) of electronic sensor such as for example biological chemistry and toward ion-sensitive has overcome the critical limitation of optical sensor.They are cheaply, and a pacing examination has just provided result within a few minutes, and the optical device that does not need well-trained technician to move this test or costliness reads this test.
FET is the natural candidate of the sensing based on electricity of electrically charged analyte, due to the dependence of the channel conduction of combination that stems from biomolecule and channel surface to grid voltage and surface charge.ISFET has developed and has exceeded 30 years, and is the reliable electronic biochemical sensor for measuring in real time the online quality monitoring such as liquid pH value and milk, beer, Yoghourt.
Recently, develop the fin type FET with nano-width raceway groove, they provide time the detection limit of parts per billion (ppb) for gas detects, and for the detection in solution provides femto mole (fM) or femto grams per milliliter, this can be comparable to state-of-the-art optical sensor.High sensitivity is owing to the nano-width (100nm or less) of fin type FET raceway groove, and they can be comparable to device Debye length and the size of biomolecule.In nano-width fin type FET, whole raceway groove can fully be modulated by the electric charge being attached in the biomolecule of gate-dielectric, and it has increased sensitivity greatly.
As described above, nano-width fin type FET has demonstrated very big potentiality becoming aspect the real low cost for meeting the application of following biological sensing, super portable and super-sensitive sensor platform.But, in fact useful for this type sensor, still there is important challenge.In the time using physiology sample such as such as whole blood, serum, saliva etc., challenge may be for example that poor stability, poor reproducibility are with poor reliability.The reliability of the surperficial difference of device itself and biologic inorganic thereof means, can not reproduce at present and make uniformly fin type FET biology sensor.
Summary of the invention
Present below and simplify general introduction, to the basic comprehension of the one or more aspects of the present invention is provided.This general introduction is not extensive overview of the present invention, and does not intend to identify key of the present invention or decisive key element, does not illustrate its scope yet.On the contrary, the primary and foremost purpose of general introduction is to present in simplified form concepts more of the present invention, as the preorder in greater detail presenting below.
Embodiments of the invention are for fin type FET biology sensor, and it comprises: at the suprabasil semiconductor layer of silicon-on-insulator (SOI); Transistor source; Transistor drain; The one or more fin type FET nano-channels that form in described semiconductor layer, wherein said nano-channel connects described transistor source and described transistor drain; Gate-dielectric, it covers a part for described one or more nano-channels; Sample raceway groove; And sensor regions, it also comprises sensor molecule, wherein said sensor molecule is coupled to described gate-dielectric, and other wherein said sensor regions is positioned at described sample raceway groove.
Another embodiment of the present invention is for the method for operation fin type FET biology sensor, and it comprises the steps: the sample with target molecule to flow through the sample raceway groove of described fin type FET biology sensor; Measure the transistorized sample electric signal of described fin type FET biology sensor; And by relevant to the concentration of specimens of described target molecule described sample electric signal.
Another embodiment of the present invention is for fin type FET array, and it comprises: multiple fin type FET biology sensor transistor units, and it has multiple sensor regions, and wherein said multiple sensor regions are positioned at same sample raceway groove.
Other embodiments of the invention are for the method for operation fin type FET biology sensor and the method for operation fin type FET biosensor array.
Brief description of the drawings
Figure 1A and 1B represent the view of fin type FET biology sensor;
Fig. 2 A is the fin type FET enhancement mode biology sensor according to the embodiment of the present invention;
Fig. 2 B is the IV curve of enhancement mode fin type FET biology sensor;
Fig. 3 A is the fin type FET depletion-mode biology sensor according to the embodiment of the present invention;
Fig. 3 B is the IV curve of depletion-mode fin type FET biology sensor;
Fig. 4 A is the fin type FET enhancement mode Schottky barrier biology sensor according to the embodiment of the present invention;
Fig. 4 B is the IV curve of enhancement mode Schottky barrier fin type FET biology sensor;
Fig. 5 A to 5C is the step that forms fin type FET biology sensor according to the embodiment of the present invention;
Fig. 6 A to 6B is according to the diagram of the fin type FET biology sensor of embodiment of the present invention formation;
Fig. 7,8 and 9 is according to the diagram of the fin type FET biology sensor with gate bias electrode of embodiment of the present invention formation;
Figure 10 uses fin type FET to detect the diagram of target molecule;
Figure 11 uses competitive binding assay and fin type FET to detect the method for target molecule;
Figure 12 is the method that uses target hapten molecule in competitive binding assay and fin type FET detection target molecule;
Figure 13 uses the electric charge PH correlativity of target molecule or the two-dimension method of dependence detection target molecule;
Figure 14 is the equipment of the electric charge PH correlativity of measurement target molecule;
Figure 15 uses its electric charge PH correlativity the method with two semi-orthogonal antibody test target molecules;
Figure 16 is according to the diagram of the fin type FET biology sensor with gate bias electrode of embodiment of the present invention formation;
Figure 17 is the fin type FET biosensor array forming according to the embodiment of the present invention; And
Figure 18 is according to the type of the fin type FET biosensor array of embodiment of the present invention formation.
Embodiment
The invention of institute's prescription is described with reference to the drawings, and wherein figure is to beginning to indicating similar or equivalent key element with similar reference number eventually.Figure not drawn on scale, and provide them just to illustrate the present invention.Several aspect of the present invention is described for diagram below with reference to example application.Should be appreciated that, set forth numerous specific detail, relation and method so that understanding of the present invention to be provided.But those skilled in the relevant art will easily recognize neither one or multiple specific detail or also can put into practice the present invention by other method.In other situation, be not shown specifically well-known structure or operation to avoid making the present invention smudgy.The present invention is not subject to the restriction of the sequence of illustrated action or event, because some actions can occur and/or occur with other action or event by different order simultaneously.And, be not need to all illustrated actions or event realize the method according to this invention opinion.
Term " sensor molecule " refers to the molecule that the molecule that will measure in sample with its concentration is selectively combined.For example, sensor molecule can be antibody, antigen, protein, acceptor, fit, peptide, DNA chain or enzyme.Sensor molecule is attached to the gate-dielectric of fin type FET.When sensor molecule is in the time that its target molecule is combined, can change the transistorized raceway groove of fin type FET electric charge around.This change of electric charge makes the electricity of fin type FET transistor channel lead change.When setover fin type FET biology sensor transistor in sub-threshold zone time, change and cause that the logarithm that fin type FET nano-channel electricity is led changes from the linearity of electric charge of target molecule that is attached to fin type FET nano-channel sensor molecule around.
Term " target molecule " refers to the molecule that its concentration will be measured in sample.Sensor molecule is combined with target molecule selectively.In many situations, can form sensor molecule such as antibody, it is to be specific to target molecule such as protein.But sometimes, as the thyroid hormone T4 in the situation that, molecule is little and uncharged, and by T4 molecule is directly injected in animal and can not forms antibody.For these situations, T4 is attached to hapten molecule, such as bovine serum albumin(BSA) (BSA), forms the target hapten molecule being injected in host animal.Immune response to T4-BSA (target haptens) molecule is strong, and the antibody forming is thus all selectable to T4-BSA molecule and independent T4 molecule.
For example, if sensor molecule is the antibody of thyroid hormone T4, it will be selectively combined to T4 hormone, although sample can contain many other similar hormone molecules, such as thyroid hormone T3.(T3 and T4 molecule are formed by 33 atoms with same structure.Unique difference is that a hydrogen atom iodine atom in T3 replaces to form T4.) in the time that sensor molecule is antibody, target molecule is called as antigen.
Term " semi-orthogonal sensor molecule " refers in sensor molecule wherein one specific and other sensor molecule cross reaction or without two or more sensor molecule of selectively presenting to target molecule to target molecule.Other sensor molecule can be attached to several molecules (except target molecule).
In the inventive embodiment of institute's prescription, target molecule can be antigen, such as for example insulin.In these application, the antibody of insulin is attached to the gate-dielectric of fin type FET biology sensor.In the time that fin type FET biology sensor is immersed in the sample that contains insulin, be attached to the insulin antibody of grid in connection with the insulin antigen in sample, lead thereby the concentration that depends on insulin antigen in sample changes fin type FET biology sensor transistorized electricity.
In other embodiment of the invention of institute's prescription, target molecule can be antibody, such as in Diagnosis of pulmonary tuberculosis.In these application, need to measure the concentration of antibody in sample.In these application, antigen can be attached to the transistorized gate-dielectric of fin type FET biology sensor, and is used as sensor molecule to detect the concentration of antibody in sample.For example, pulmonary tuberculosis antigen can be attached to the gate-dielectric of fin type FET biology sensor.In the time that fin type FET biology sensor is immersed in the sample that contains pulmonary tuberculosis antibody, antibody in sample is attached to the pulmonary tuberculosis antibody on gate-dielectric, leads thereby the concentration that depends on pulmonary tuberculosis antibody in sample changes fin type FET biology sensor transistorized electricity.
The parameter that " signal " of term fin type FET biology sensor refers to the electrical quantity of direct measurement and/or draw from the electrical quantity of sensor device of measuring.The detection signal of sensor can be with many forms.For the signal of direct measurement, can there is several different biasings and configuration.A kind of mode is with known voltage biasing source electrode and drain electrode, and with another known voltage offset gate electrode, measures drain current at sensing experimental session.Another kind of mode is with current source biasing source electrode and drain electrode, and with known voltage offset gate electrode, measures drain voltage at during sensing.The third mode is with known voltage biasing source electrode and drain electrode, at the voltage range interscan gate electrode voltage of selecting, and measures drain current simultaneously, and then generates transistorized standard I-V curve.
Signal can be also the parameter of indirectly measuring or drawing from direct measurement result, as summarized above.Here provide several examples.The first, with the electrical quantity of measuring, the change that can draw these parameters by deduct measured value from the initial value of measuring or measure with master sample before sensing.Also can be by relative changes be drawn to the number percent of change divided by initial value.In addition, can be by the drain current of measurement is shown to transistor electricity leads divided by drain voltage, or can be by the drain current of measurement is drawn to transistorized mutual conductance divided by the voltage of gate electrode.With transistor I-V curve of measuring, change or the skew etc. that can extract threshold voltage and threshold voltage.All these direct or indirect transistor signals all can be used for analyzing and testing result, and relevant to the concentration of target molecule.In order to simplify, in the following embodiments, we use transistorized electricity to lead as the exemplary signals in sensor device.
Term " fin type FET biosensor array " refers to have the transistorized fin type of more than one fin type FET biology sensor FET biosensor arrangement, and wherein the transistorized sensor region of each fin type FET biology sensor is exposed to same sample.In the time that sample is imported into fin type FET biosensor array, it is all immersed in the transistorized sensor region of all fin type FET biology sensors in fin type FET biosensor array.Fin type FET biology sensor transistor can have different fin width to detect different concentration of target molecules scopes separately, can there is attached different sensors molecule to detect different target molecule in sample, or can have and be attached to the different transistorized semi-orthogonal antibody of fin type FET biology sensor.
For most of target molecules, can directly measure the concentration in sample, as illustrated in Figure 10 A and 10B.As shown in FIG. 10A, if the concentration of target molecule 1006 is low, a few target molecule 1006 is in connection with to fixed sensor molecule 1004 on fin 1002.Due to seldom target molecule-sensor molecule compound formation, therefore fin channel conduction changes very little.
But if the target molecule 1006 that sample contains high concentration, as shown in Figure 10 B, many target molecule-sensor molecule compounds 1008 form, and cause the large change of fin channel conduction.That in the direct measurement mensuration of leading as the fin electricity that fin FET biology sensor transistor is measured, electric current is directly proportional to the concentration of target molecule in sample in change.
In some cases, target molecule may be little, or has inadequate electric charge, leads thereby detect by sensitivity with required the electricity that the required amount of concentration of target molecules in sample changes fin FET biology sensor raceway groove.For these situations, target molecule can be attached to fin, as shown in Figure 11 A and 11B, and can use the competitive binding of sensor molecule.
As shown in Figure 11 A, target molecule 1106 can be attached to the fin 1102 of fin FET biology sensor.Then,, before fin is immersed in sample, add the sensor molecule of known quantity 1104 to sample solution.If sample contains some target molecules 1106, as shown in Figure 11 A, many sensor-target molecule compound 11s 08 will be formed on the surface of fin 1102.Because sensor molecule is carried a large amount of electric charges conventionally, the electricity that has therefore greatly changed fin raceway groove is led.
But, as shown in Figure 11 B, if the target molecule 1106 that sample solution contains quite large concentration, be added to many in the sensor molecule 1104 of known quantity of sample and will in solution, form sensor-target molecule compound 11 08, thereby leave little free sensor molecule 1104 and be attached to sensor-target molecule compound 11 08 of fin 1102 to form, and change fin electricity and lead.In sensor molecule competitive binding assay, in the change that fin electricity is led and sample, the concentration of target molecule is inversely proportional to.
Alternatively, as shown in Figure 12 A and 12B, in the time that target molecule 1206 is attached to sensor molecule 1204, if described target molecule 1206 is too little or lack sufficient electric charge, and the electricity that can not change fin FET biology sensor is led, can add to sample the target-hapten molecule 1210 of concentration known.As shown in Figure 12 A, if sample has low target molecular conecentration 1206, many in connection with the sensor molecule 1204 to fin in target-hapten molecule 1210, form sensor-molecule-target-hapten molecule compound 1212.Because haptens carries a large amount of electric charges conventionally, the electricity that therefore can greatly change fin raceway groove is led.
Alternatively, as shown in Figure 12B, if sample contains high concentration of target molecules 1206, little target-hapten molecule 1210 can be attached to fixed sensor molecule 1204 on fin, thereby causes the little change that fin electricity is led.In this type of target-hapten molecule competitive binding assay, what in sample, the concentration of target molecule and fin electricity were led changes over inverse ratio.
Except the sensor signal of measuring, also can use pH value as another parameter, carry out the two-dimensional detection of realize target molecule.As shown in Figure 13, scan the pH value 1306 of the sample solution that contains for example CAA24102 of target molecule at sensing experimental session, can generate the electric charge 1308 of target molecule to Figure 130 2 of solution pH value 1306.Drawing before Figure 130 2, can lead or variation draws the electric charge 1308 of target molecule from the fin type FET electricity of measuring.For such as CAA32220 of different target molecule, in sample solution, can carry out the similar experiment of PH scanning, and generate another Figure 130 4 of the second target molecule CAA32220.Can use Figure 130 2 to 1304 shape information, such as slope, crest and trough, clearly distinguish the target molecule of two types, it provides fingerprint signature significantly to improve detection specificity.
In an embodiment of the present invention, figure 14 illustrates the setting that realizes two dimension test.The sample solution that contains target molecule 1402 is prepared to has low pH value, and is connected to liquor pump or valve 1408.Same sample solution is prepared to has high pH value 1404, and is connected to another liquor pump or valve 1406.These two liquid inlets 1406 and 1408 are integrated into the same raceway groove of fin type FET sensor 1410.Control synergistically high PH 1412 and low PH 1414 and enter the solution flow rate in sensor 1410.For example, if scan high PH flow rate 1412 from 0 to maximum linear, scan low PH flow rate 1414 from being up to 0 with same linearity, it causes from low 1402 to high 1404 continuous and linear sweep pH values in sample solution simultaneously, keeps the target molecule of same concentration simultaneously.Electricity at PH scan period continuous coverage fin type FET is led, and makes to generate electricity and leads the figure to pH value, and can draw the figure of electric charge to pH value, as shown in Figure 13.
Also can be by strengthening the specificity of detection as the target molecule electric charge of the function of solution PH for same target molecule by polytype semi-orthogonal sensor molecule, as shown in the fin type FET biosensor array shown in figure and Figure 18 in Figure 15 A and 15B.For example, the specific antibody of target molecule height is attachable to the first fin type FET biology sensor 1802 in fin type FET biosensor array 1800, and for obtaining the first electric charge-PH Figure 150 4, it is the process of Figure 13 and then.Same target molecule cross reaction or unspecific another antibody are attachable to the second fin type FET biology sensor 1804 in same sample raceway groove 1806, and for obtaining another electric charge-PH Figure 150 2.Because the electric charge of target molecule-sensor molecule compound depends on the interactive binding specificity of Ag-Ab and cross reactivity, therefore two Figure 150 2 and 1504 have different shapes.Then, for identical pH value, can draw the charge value of two semi-orthogonal sensor molecule-target molecule compounds, as shown in Figure 15 B, specific associated value 1504 as X-axis to the associated value 1502 of cross reaction as Y-axis.The curve of the target molecule 1510 forming in semi-orthogonal collection of illustrative plates can be used as the specific and fingerprint accurately of the height of target molecule, because the specific and nonspecific combining information that it contains target molecule.The target molecule 1512 of another type or other molecule all can cause that to any nonspecific combination of sensor some electricity lead change, but will have different positions and shape in semi-orthogonal collection of illustrative plates.This mode can make it possible to accurately detect target molecule, and wherein false positive has reduced a lot.
Figure 1A illustrates the fin type FET biology sensor transistor with parallel multiple fin type FET nano-channels 108.Fin type FET sensor crystal pipe is structured in semiconductor-on-insulator (SOI) substrate, this semiconductor-on-insulator (SOI) substrate is made up of substrate 100 and buried oxide (BOX) layer 102, and it has the single-crystal semiconductor layer forming therein on the transistorized top of fin type FET biology sensor.Fin type FET biology sensor transistor is made up of source electrode 104 and drain electrode 106, has the multiple fin type FET nano-channels 108 that connect source electrode 104 and drain electrode 106.The width 120 of nano-channel 108 is preferably less than about semi-conductive Debye length, for peak response.Debye length is approximately equal to the required distance of the static electric charge of mobile carrier screening.In the time that target molecule electric charge spreads all over the whole width of fin type FET nano-channel and length modulated electricity and leads, realize the maximum that fin type FET nano-channel electricity leads and change.
As in Figure 1B by as shown in the xsect of fin type FET nano-channel, gate-dielectric 110 be formed on fin type FET nano-channel 108 above, and sensor molecule 112 is attached to gate-dielectric 110.Fin type FET nano-channel 108 sample solution around can contain many different molecule 1s 14 and 116, and it comprises target molecule 118.In embodiment, use antibody and antigen illustrated embodiment below.Antibody 112 is only specific to target molecule 118, and will only be attached to that antigen 1 18.Charge conventionally to antigen 1 18, therefore when they are attached to antibody 112, the electric charge on their change fin type FET nano-channel 108 grids, and the electricity that therefore changes fin type FET nano-channel 108 is led.This has changed the electric current that flows to drain electrode in fin type FET biology sensor transistor from source electrode.There is the sample of higher concentration antigen in connection with more antigen, and therefore in the transistorized electricity of sensor fin type FET is led, cause larger change.The change of the electric current by fin type FET biology sensor therefore can be relevant to the change of the antigen concentration in sample.The transistorized sensitivity of fin type FET biology sensor depends on the S/V of fin type FET nano-channel, and depends on transistorized signal to noise ratio (S/N ratio).Therefore, can be by reducing the width of fin and highly increasing sensitivity; Also can pass through to increase the quantity of fin type FET nano-channel, or reduce the length of nano-channel, due to the signal to noise ratio (S/N ratio) increasing, and strengthen sensitivity.And the quantity that increases fin type FET also can aggrandizement apparatus homogeneity and stability, owing to having reduced the discrete doping effect in fin.
In an embodiment of the present invention, fin type FET transistor biology sensor can be enhancement mode MOSFET, depletion-mode MOSFET or Schottky-barrier MOSFET.Embodiment nmos enhancement mode fin type FET transistor has been shown in Fig. 2 A.Substrate 202 in example embodiment and fin type FET nano-channel 204 by light dope p-type monocrystalline silicon.Source electrode 206 and drain electrode 208 diffusions have been heavily doped N-shaped 210.
In Fig. 2 B, illustrate that the transistorized electric current 216 of enhancement mode nmos fin type FET is to grid voltage 214 curves.When setover nmos transistor in sub-threshold slope district 212 time, the little change of grid voltage 214 causes the large change of source electrode to drain current 216.Although in order illustrating, to have used nmos fin type FET enhancement mode transistors, also can to have used pmos fin type FET enhancement mode transistors.
Embodiment pmos fin type FET depletion-mode transistor has been shown in Fig. 3 A.Substrate 302 and fin type FET nano-channel 304 by light dope p-type monocrystalline silicon.Source electrode 306 and drain electrode 308 diffusions have been heavily doped p-type 310.
In Fig. 3 B, illustrate that the transistorized electric current 316 of pmos fin type FET depletion-mode is to grid voltage 314 curves.When setover pmos transistor in sub-threshold slope district 312 time, the little change of grid voltage 314 causes the large change of source electrode to drain current 316.Although in order illustrating, to have used pmos fin type FET depletion-mode transistor, also can to have used nmos fin type FET depletion-mode transistor.
Embodiment pmos enhancement mode Schottky barrier fin type FET transistor has been shown in Fig. 4 A.Substrate 402 and fin type FET nano-channel 404 by light dope p-type monocrystalline silicon.Source electrode 406 and drain electrode 408 diffusions also by light dope p-type monocrystalline silicon, it has been formed to Schottky Barrier Contact.Described Schottky Barrier Contact can form by following: plated metal such as nickel, titanium or platinum, and then in inert atmosphere (such as forming gas, hydrogen, nitrogen, argon or their potpourri), give contact annealing with the temperature within the scope of 300 ° of C to 600 ° of C.
In Fig. 4 B, illustrate that the transistorized electric current 416 of enhancement mode pmos fin type FET is to grid voltage 414 curves.As shown in Figure 4 B, Schottky barrier enhancement mode transistors all has sub-threshold slope in negative-gate voltage 418 and positive gate voltage 412nd district.This provides the additional advantage that can all operate Schottky barrier fin type FET comparative result in Liang Gezi threshold slope district.In addition,, for given sensor molecule, detection target molecule can have the sensitivity of increase in one of Liang Gezi threshold slope district 418 or 412.Although for illustrated embodiment, used pmos enhancement mode schottky transistor, also can use nmos enhancement mode schottky transistor.
Can significantly improve sensitivity, accuracy and the repeatability of fin type FET nano-channel biology sensor, as shown in illustrated embodiment coating process in Fig. 5 A to 5C.
In Fig. 5 A, sensor region photoetching agent pattern 512 covers the sensor regions 516 of fin type FET transistor biology sensor 502.Fin type FET biology sensor 504, the 506 He510 districts that are exposed can be coated with anti-adhesive protection molecule, such as self-assembled monolayer, fluorine carbon molecule or thin layer resist such as the tygon (methyl methacrylate) of the self-assembled monolayer of polyglycol (PEG) end-blocking, benzene end-blocking (PMMA) or S1813 (from the STO-609-acetic acid of Sigma-Aldrich) etc.The sensor region 516 being covered by sensor region photoengraving pattern 512 only occupies can be by the sub-fraction of the surf zone of sample solution or sample gas contact.If target molecule is adsorbed to the surface of sensor region outside and is absorbed, can from sample solution or gas, remove a large amount of target molecules, thereby changed concentration of specimens before it arrives sensor region.This can cause and change and error in the measurement of concentration of target molecules.By the surface with anti-adhesive protection molecule coating sensor region outside, can significantly strengthen reproducibility, reliability and the sensitivity of fin type FET biology sensor.
Fig. 5 B shows fin type FET biology sensor 502, and wherein the region 514 of sensor region 516 outsides is coated with anti-adhesive protection molecule, and has removed photoetching agent pattern 512.Example embodiment shows a part for the fin type FET nano-channel being included in sensor region, but in sensor region, can comprise the whole length of fin type FET nano-channel.
As shown in Figure 5 C, then sensor region 516 is coated with sensor molecule 518, such as antibody.In example embodiment, by fin type FET biology sensor 502 is immersed in the solution that contains cross-linker molecules, first cross-linker molecules such as 11-(triethoxy) hendecanal (TESU) is attached to sensor region.Solvent for cross-linker molecules can be toluene.Next,, by fin type FET biology sensor 502 is submerged in the buffer solution that contains sensor molecule, sensor molecule such as antibody can be attached to cross-linker molecules in conjunction with position.If the crosslinking chemical of use has not retained in conjunction with position, then fin type FET biology sensor 502 can be immersed in the buffer solution that contains crosslinking chemical blocking agent molecule, described crosslinking chemical blocking agent molecule is attachable to the cross-linker molecules of use not in conjunction with position, blocks thus them.This has stoped the non-target molecule in sample to be attached to these positions.The non-target molecule that is attached to cross-linker molecules can change the electric charge on the grid of fin type FET nano-channel, and it causes variability and optionally loses.Block the cross-linker molecules of use not and improved sensitivity, selectivity and the accuracy of fin type FET biology sensor 502 in conjunction with position.
Fig. 6 A shows the embodiment fin type FET biology sensor 602 after other processing.The dielectric layer 604 with sample raceway groove 606 be formed on fin type FET biology sensor 602 above.Dielectric can be silicon dioxide or silicon nitride or plastics, such as polyimide.Liquid or gaseous state sample can flow through sample raceway groove 606, and above sensor region 618 in sample raceway groove 606.Outside but can be coated with anti-adhesive protection molecule at the surf zone of sample raceway groove 606 inside at sensor region 618.To the contact 608 of the source electrode 610 of fin type FET biology sensor 602 with 612 form by dielectric 604 to contacting of drain electrode 614, and be filled with conductive material, such as CVD-W, copper or aluminium alloy.Although sample raceway groove 606 is shown in pipeline mobile above sample areas 606 in this embodiment, also can use other sample channel arrangements, such as the open top trap 620 in Fig. 6 B.
In the embodiment shown in Fig. 7, offset line 704 extends in sample raceway groove 708.Can apply voltage (Vgate) 706 so that fin type FET nano-channel 710 is biased in sub-threshold zone to offset line 704.The liquid sample that line is conduction for liquid is active electrode, but may not be active electrode for gaseous state sample.Offset line 704 is preferably formed by platinum or silver/agcl mixt.
Figure 8 illustrates another example embodiment on fin type FET sensor region with biasing plate 804.Can apply voltage (Vgate) 806 so that fin type FET nano-channel 810 is biased in sub-threshold zone to biasing plate 804.Biasing plate 804 may be originally all active electrode for the gentle aspect of liquid.For liquid sample, biasing plate is preferably formed by platinum or silver/agcl mixt.For gaseous state sample, biasing plate can be formed by any metal material not reacting with gaseous state sample.
In Fig. 9, illustrate fin type FET nano-channel 910 is biased to another embodiment method in sub-threshold zone.Can use BOX 912 as gate-dielectric, basad 904 apply bias voltage 906 so that fin type FET nano-channel 910 is biased in sub-threshold zone.For this biasing means, thinner BOX 912 is favourable, because bias electrode 904 is put to obtain more close fin type FET nano-channel by it.Originally all can use this biasing means for the gentle aspect of liquid.This method can be the method for optimizing for gaseous state sample.
In Figure 16, illustrate fin type FET nano-channel 1602 is biased to the other embodiment method in sub-threshold zone.During processing, the electrode 1610 of micro-patterning can be formed on the top surface of SOI substrate 1600, and on fin type FET biology sensor side, extends in sample raceway groove 1612.Electrode 1610 can be by doped silicon; Silicide such as titanium, nickel or platinum; Or metal forms.The electrode 1610 that contact 1608 can be formed as micro-patterning contacts 1604 source electrode and the drain regions 1606 that are formed as fin type FET biology sensor simultaneously.
Biology sensor fin type FET array 1700 has been shown in Figure 17, and it can realize the concentration of measurement target molecule on several orders of magnitude.Biology sensor fin type FET array 1700 is made up of several biology sensor fin type FET transistors 1702,1704,1706 in sample raceway groove 1708 and same sample raceway groove 1708 with the fin width of certain limit.For example, the fin type FET transistor 1702 with wide fin width can be optimized to measure micromole and arrive the concentration of target molecules within the scope of millimolar concentration, the fin type FET transistor 1704 with middle fin width can be optimized to be measured in nanometer mole to the concentration of target molecules within the scope of micro-molar concentration, and the fin type FET transistor 1706 with narrow fin width can be optimized to and measures in femto mole to the concentration of target molecules within the scope of nanometer volumetric molar concentration.In order to illustrate, use the fin type FET biosensor array 1700 with three fin type FET biology sensor transistors (thering is separately different fin width).The transistorized fin type of the fin type FET biology sensor FET biosensor array with varying number can be optimized to for all types of target molecular conecentration scope.
In the embodiment fin type FET biosensor array 1800 shown in Figure 18, first sensor molecule is attachable to the gate-dielectric of the first fin type FET biology sensor transistor 1802, and the second sensor molecule is attachable to the gate-dielectric of the second fin type FET biology sensor transistor 1804.In this way, can in the sample in sample raceway groove 1806, measure the concentration of two different target molecules.Can use fin type FET biology sensor more than two (each have the different sensors molecule that is attached to gate-dielectric) to measure in sample the concentration more than the target molecule of two.
Although various embodiment of the present invention described above, should be understood that only unrestrictedly by example to present them.Can, according to the numerous changes made disclosed embodiment that disclose herein, not depart from the spirit or scope of the present invention.Thus, range of the present invention and scope should not be subject to the restriction of any embodiments described above.On the contrary, should limit scope of the present invention according to enclose claim and equivalent thereof.

Claims (47)

1. a fin type FET biology sensor, comprising:
At the suprabasil semiconductor layer of silicon-on-insulator (SOI);
Transistor source;
Transistor drain;
The one or more fin type FET nano-channels that form in described semiconductor layer, wherein said nano-channel connects described transistor source and described transistor drain;
Gate-dielectric, it covers a part for described one or more nano-channels;
Sample raceway groove; And
Sensor regions, it also comprises sensor molecule, wherein said sensor molecule is coupled to described gate-dielectric, and other wherein said sensor regions is positioned at described sample raceway groove.
2. fin type FET biology sensor as claimed in claim 1, also comprises that the surperficial anti-adhesive of the outside described sample raceway groove in the described sensor regions of coating is protected molecular layer.
3. fin type FET biology sensor as claimed in claim 2; wherein, described anti-adhesive protection molecular layer by self-assembled monolayer, fluorine carbon molecule or thin layer resist such as the tygon (methyl methacrylate) of the self-assembled monolayer of polyglycol (PEG) end-blocking, benzene end-blocking (PMMA) or S1813 form.
4. fin type FET biology sensor as claimed in claim 1, wherein, described sensor molecule is antibody, antigen, protein, acceptor, fit, peptide, DNA chain or enzyme.
5. fin type FET biology sensor as claimed in claim 1, wherein, described sensor molecule is antibody.
6. fin type FET biology sensor as claimed in claim 1, wherein, described sensor molecule is antigen.
7. fin type FET biology sensor as claimed in claim 1, also comprises bias electrode.
8. fin type FET biology sensor as claimed in claim 7, wherein, described bias electrode is offset line, it extends in described sample raceway groove; Biasing plate, it is arranged in described sample raceway groove and it is placed on described sensor regions; SOI substrate, it comprises buried oxide (BOX) layer; Or on the top surface of SOI substrate and be positioned at the metal electrode of micro-pattern on described nano-channel side.
9. fin type FET biology sensor as claimed in claim 7, wherein, described bias electrode is formed by platinum or silver/agcl mixt.
10. fin type FET biology sensor as claimed in claim 1, wherein, described fin type FET is nmos or pmos enhancement mode transistors.
11. fin type FET biology sensors as claimed in claim 10, wherein, described fin type FET is nmos enhancement mode transistors, wherein said semiconductor layer has and is less than about 1E18/cm 3p-type doping; And described transistor source and described transistor drain have and are greater than about 1E19/cm 3n-shaped doping.
12. fin type FET biology sensors as claimed in claim 10, wherein, described fin type FET is pmos enhancement mode transistors, wherein said semiconductor layer has and is less than about 1E18/cm 3n-shaped doping; And described transistor source and described transistor drain have and are greater than about 1E19/cm 3p-type doping.
13. fin type FET biology sensors as claimed in claim 1, wherein, described fin type FET is nmos or pmos depletion-mode transistor.
14. fin type FET biology sensors as claimed in claim 13, wherein, described fin type FET is nmos depletion-mode transistor, wherein said semiconductor layer has and is less than about 1E17/cm 3n-shaped doping; And described transistor source and described transistor drain have and are greater than about 1E19/cm 3n-shaped doping.
15. fin type FET biology sensors as claimed in claim 13, wherein, described fin type FET is pmos depletion-mode transistor, wherein said semiconductor layer has and is less than about 1E17/cm 3p-type doping; And described transistor source and described transistor drain have and are greater than about 1E19/cm 3p-type doping.
16. fin type FET biology sensors as claimed in claim 1, wherein, described fin type FET is nmos or pmos Schottky barrier enhancement mode transistors.
17. fin type FET biology sensors as claimed in claim 16, wherein, described fin type FET is nmos Schottky barrier enhancement mode transistors, wherein said semiconductor layer has and is less than about 1E18/cm 3p-type doping; And described transistor source and described transistor drain form the Schottky contacts with described semiconductor layer.
18. fin type FET biology sensors as claimed in claim 16, wherein, described fin type FET is pmos Schottky barrier enhancement mode transistors, wherein said semiconductor layer has and is less than about 1E18/cm 3n-shaped doping; And described transistor source and described transistor drain form the Schottky contacts with described semiconductor layer.
19. fin type FET biology sensors as claimed in claim 1, wherein, described gate-dielectric is by silicon dioxide, silicon nitride, Al 2o 3, HfO 2or silicon oxynitride composition, and described gate-dielectric has the thickness of 0.5-20nm.
20. fin type FET biology sensors as claimed in claim 1, wherein, described sensor molecule is used cross-linker molecules to be coupled to described gate-dielectric.
21. fin type FET biology sensors as claimed in claim 20, wherein, described cross-linker molecules is to have 2 to 20 carbon carbon bonds of attached described sensor molecule and the silane of functional group.
22. fin type FET biology sensors as claimed in claim 1, wherein, described sample raceway groove is sample pipeline or sample trap.
23. 1 kinds operate the method for fin type FET biology sensor, comprise the steps:
The sample with target molecule is flowed through to the sample raceway groove of described fin type FET biology sensor;
Measure the transistorized sample electric signal of described fin type FET biology sensor; And
By relevant to the concentration of specimens of described target molecule described sample electric signal.
24. methods as claimed in claim 23, comprise the steps:
The first sample of first normal concentration with described target molecule is flowed through to described sample raceway groove, and measure the first master sample value of electrical signals;
The second sample of second normal concentration with described target molecule is flowed through to described sample raceway groove, and measure the second master sample value of electrical signals;
By described the first and second normal concentrations on described first on the first figure axle and described the second standard electric signal value and the second figure axle, drawing standard curve map; And
By drawing described sample electric signal by relevant to described concentration of specimens described sample electric signal on described canonical plotting.
25. methods as claimed in claim 23, comprise the steps:
The antigen of the grid that is coupled to described fin type FET biology sensor is provided to fin type FET biology sensor; And
Add the antibody of fixed concentration to each sample, wherein before the described step of described sample that flows, described antibody is specific to described antigen.
26. methods as claimed in claim 23, comprise the steps:
The target haptens of the grid that is coupled to described fin type FET biology sensor is provided to fin type FET biology sensor; And
Add the antibody of fixed concentration to each sample, wherein before the described step of described sample that flows described antibody to described target haptens be specific to described target molecule.
27. methods as claimed in claim 23, comprise the steps:
The antibody of the grid that is coupled to described fin type FET biology sensor is provided to fin type FET biology sensor; And
Add the target hapten molecule of fixed concentration to each sample, wherein before the described step of described sample that flows, described antibody is specific to described target hapten molecule, and is specific to described target molecule.
28. methods as claimed in claim 23, wherein, described sample electric signal is the drain electrode of described fin type FET or source current, I-V curve, grid voltage, drain voltage.
29. 1 kinds of fin type FET arrays, comprising:
Multiple fin type FET biology sensor transistor units, have multiple sensor regions, and wherein said multiple sensor regions are positioned at same sample raceway groove.
30. fin type FET arrays as claimed in claim 29, wherein, described multiple fin type FET biology sensor transistors have different channel widths, and sensor molecule is attached to each in described multiple sensor region.
31. fin type FET arrays as claimed in claim 29, also comprise:
The first fin type FET biology sensor transistor, has the first channel width being chosen to for having the target molecule of concentration from 0.1 femto mole to nanometer mole and carry out the sensing with optimum sensitivity and dynamic range;
The second fin type FET biology sensor transistor, has the second channel width being chosen to for having concentration and carry out from nanometer mole to micromolar target molecule the sensing with optimum sensitivity and dynamic range; And
The 3rd fin type FET, has the triple channel width being chosen to for having the target molecule of concentration from micromole to mM and carry out the sensing with optimum sensitivity and dynamic range; Wherein said the first channel width is narrower than described the second channel width, and wherein said the second channel width is narrower than described triple channel width.
32. fin type FET arrays as claimed in claim 29, also comprise:
The first fin type FET biology sensor transistor, contains the optionally first antibody having target molecule; And
The second fin type FET biology sensor transistor, contains the second antibody with the cross reaction to described target molecule.
33. fin type FET arrays as claimed in claim 29, also comprise:
The first fin type FET biology sensor transistor, contains the optionally first sensor molecule having first object molecule; And
The second fin type FET biology sensor transistor, contains optionally the second sensor molecule having the second target molecule.
34. 1 kinds operate the method for fin type FET biology sensor, comprise the steps:
The sensor region of described fin type FET biology sensor is immersed in first sample solution with the target molecule that a PH contains a concentration, and measures the first fin type FET transistor signal; And
The described sensor region of described fin type FET biology sensor is at least immersed in second sample solution with the described target molecule that the 2nd PH contains described concentration, and measures the second fin type FET transistor signal.
35. methods as claimed in claim 34, comprise the steps:
The described sensor region of described fin type FET biology sensor is immersed in multiple sample solutions with the described target molecule that multiple PH contain described concentration, and measures multiple fin type FET transistor signals; And
Prepare the figure of described multiple PH to described multiple fin type FET transistor signals.
36. methods as claimed in claim 34, wherein, described multiple PH change in a continuous manner.
37. methods as claimed in claim 34, wherein, PH scope and pH value cover the isopotential point (pI) of protein.
38. methods as claimed in claim 34, wherein, described first and described the second fin type FET transistor signal drive current, drain voltage, grid voltage, electricity of comprising described fin type FET biology sensor transistor signal led, mutual conductance and relative changes.
39. methods as claimed in claim 34, comprise the steps:
Fill the first reservoir with the solution with the target molecule that high PH contains a concentration;
Fill the second reservoir with the solution with the described target molecule that low PH contains described concentration;
Described first reservoir with the first pump is coupled to the sample raceway groove of fin type FET biology sensor;
Described second reservoir with the second pump is coupled to described sample raceway groove;
Operate described the first pump and described the second pump with cooperative mode, thereby the described solution with the PH changing from low to high or from high to low in even mode is delivered to described sample raceway groove.
40. methods as claimed in claim 34, also comprise the steps:
The two-dimension analysis of carrying out described target molecule also comprises the steps:
Measure the change at the described fin type FET transistor signal of a PH; And
Measure the change at the described fin type FET transistor signal of multiple PH;
At fin type FET transistor signal described in the first plot on X axis of figure, and at multiple PH described in the second plot on X axis of figure;
Determine the concentration of described target molecule; And
Determine the biomolecule type of described target molecule.
41. 1 kinds operate the method for fin type FET biosensor array, comprise the steps:
First kind sensor molecule is provided to the first fin type FET biology sensor transistor;
Second Type sensor molecule is provided to the second fin type FET biology sensor transistor;
By described first and described the second fin type FET biology sensor transistor be immersed in the sample solution of the target molecule that contains a concentration;
Measure the transistorized the first transistor signal of described the first fin type FET biology sensor; And
Measure the transistorized transistor seconds signal of described the second fin type FET biology sensor.
42. methods as claimed in claim 41, comprise the steps:
By relevant to the concentration of first object molecule described the first transistor signal; And
By relevant to the concentration of the second target molecule described transistor seconds signal.
43. methods as claimed in claim 41, also comprise the steps:
By described first and described the second fin type FET biology sensor transistor be immersed in multiple sample solutions with the target molecule that multiple pH values contain a concentration;
For each of described sample solution measure described first and described the second fin type FET biology sensor transistor in each multiple transistor signals; And
Draw the figure of described multiple PH and described multiple fin type FET transistor signals.
44. methods as claimed in claim 43, wherein, described sensor molecule is all specific to same target molecule.
45. methods as claimed in claim 43, wherein, described sensor molecule is semi-perpendicular for target molecule.
46. methods as claimed in claim 43, wherein, by the drafting transistorized described multiple signals of described the first fin type FET biology sensor of described first kind sensor molecule coating and the transistorized described multiple signals of described the second fin type FET biology sensor with described Second Type sensor molecule coating, generate described figure.
47. methods as described in claim 41 and 43, also comprise the steps:
Calculate the electric charge of the described target molecule of each PH in described multiple PH; And
Prepare the figure of described multiple PH about the described electric charge of described target molecule.
CN201180057335.1A 2010-09-29 2011-09-28 Fin-FET biosensor with improved sensitivity and selectivity Pending CN103842817A (en)

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